The main objectives of this proposal are to study: 1. the regional differences in the susceptibility of aorta to spontaneous atherosclerosis and 2. the structural and chemical response of aortic regions to hypertension. Recent studies in the White Carneau pigeon from our laboratory indicated that: a. despite the presence of intimal cushions in the aorta at birth, classic atherosclerotic plaques develop in an area across from these cushions and b. intimal thickness in the lesion area does not precede, but rather follows intimal fat accumulation. This provides us with an unusual opportunity to study the differences in the structure, chemistry, and metabolism of intimal cushion area and lesion area in the same aorta exposed to an identified plasma milieus and also investigate the effect of a single risk factor, i.e., hypertension. Studies are proposed to compare the: a. nature and subcellular distribution of lipids, b. synthesis of squalene, cholesterol and cholesteryl esters, c. hydrolysis of cholesteryl esters, and d. biosynthesis of specific prostaglandins between the two areas under normal and hypertensive conditions. These studies will reveal structural and metabolic differences in the response of intimal cushions and lesion areas to hypertension, and explore the significance of prostaglandin system in these responses.